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Acute Lymphoblastic Leukemia, in RelapsePhase 2/3GRASPIVOTALLNCT01518517

GRASPA (Erythrocytes Encapsulating L-asparaginase) in Patients With Relapse of Acute Lymphoblastic Leukemia

A Phase 2/3 study testing GRASPA and L-asparaginase in people with Acute Lymphoblastic Leukemia, in Relapse, run by ERYtech Pharma at 28 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent… Read more about this study

Who is it for?
Ages 1 year to 55 years
Conditions the study is for
Acute Lymphoblastic Leukemia, in Relapse
What is being tested?
GRASPA and L-asparaginase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
28 sitesin 2 countries
Study dates
Dec 2009to Oct 2016
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient from 1 to 55 years old (Children and adolescents from 1 to 17 years/ Adults from 18 to 55 years)
  • Patients with 1st ALL relapse, which could be either isolated bone marrow relapse, or combined (medullary and extra-medullary) relapse, or extra-medullary isolated relapse; or lymphoblastic lymphoma (excepted Burkitt lymphoma) OR Failure to ALL first line treatment (no complete remission obtained)
  • Patient previously treated with free E.Coli L-asparaginase form or pegylated one
  • Performance Status ≤ 2 (WHO score)
  • Patient informed and consent provided (the 2 parents need to consent when children are below 18)

Who cannot join

  • ALL t(9;22) and/or BCR-ABL positive (Philadelphia chromosome positive)
  • Patient with 2nd relapse and over
  • Women of childbearing potential without effective contraception as well as pregnant or breast feeding women
  • Patient unable to receive treatments used in global chemotherapy protocols, due to general or visceral conditions such as:Severe cardiac impairment (NYHA grade 3 or 4 cardiomyopathy)/Serum creatinine 2 x ULN unless related to ALL /ALT or AST 5 x ULN unless related to ALL /Pancreatitis history /Other malignancy that ALL / Severe Infection, HIV positive, active hepatitis related to B or C virus infection / Trisomy 21 / Other serious conditions according to investigator's opinion
  • Known grade 4 allergic reaction to E.Coli L-asparaginase (according NCI-CTCAE, Version 3.0)
  • History of grade 3 transfusional incident
Show all 11Show fewer
  • Presence of specific anti-erythrocyte antibodies preventing from getting a compatible erythrocyte concentrate for the patient
  • Patient under concomitant treatment likely to cause hemolysis
  • Patient undergoing yellow fever vaccination
  • Patient under phenytoin treatment
  • Patient included in previous clinical study less than 6 weeks ago

Trial locations and contacts

28 sites in 2 countries.

28 sites in 2 countries

France26 sites

  • Chu D'Angers

    Angers

  • Hopital Saint Jacques

    Besançon

  • Hopital Pellegrin Enfants

    Bordeaux

  • Chu Estaing

    Clermont-Ferrand

  • Hopital Henri Mondor

    Créteil

  • Chu Grenoble

    Grenoble

  • Chru Lille - Hop Jeanne de Flandres

    Lille

  • Institut Hematologie Oncologie Pediatrique

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • Hopital Mere Enfant

    Nantes

  • Hotel Dieu

    Nantes

  • Hopital de L'Archet 2

    Nice

  • Hopital Armand Trousseau

    Paris

  • Hopital Robert Debre

    Paris

  • Hopital Saint Louis

    Paris

  • Hopital Haut-Leveque

    Pessac

  • Hopital Lyon Sud

    Pierre-Bénite

  • Chru Hopital Sud

    Rennes

  • Centre Henri Becquerel

    Rouen

  • Chu Hopital Nord

    Saint-Etienne

  • Institut Cancerologie de La Loire

    Saint-Priest-en-Jarez

  • Hopital de Hautepierre

    Strasbourg

  • Chu de Toulouse Enfants

    Toulouse

  • Hotel Dieu

    Valenciennes

  • Hopital Brabois Enfants

    Vandœuvre-lès-Nancy

  • Hopital de Brabois

    Vandœuvre-lès-Nancy

Other trials in France

Belgium2 sites

  • Hopital Des Enfants Reine Fabiola

    Brussels

  • Chr de La Citadelle

    Liège

Other trials in Belgium

About this study

Official title: Phase 2/3 Study Evaluating Efficacy and Safety of Erythrocytes Encapsulating L-asparaginase (GRASPA)Versus Reference L-asparaginase Treatment in Combination With Standard Polychemotherapy in Patient With First Recurrence of Philadelphia Negative Acute Lymphoblastic Leukemia

Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA improves pharmacokinetics, tolerability and maintain circulating asparaginase activity due to the protective barrier of the erythrocyte membrane.

This study is run to confirm the benefit/risk profile of GRASPA at 150 IU/kg in combination with the COOPRALL regimen in adults and children patients with relapsed ALL, with or without known hypersensitivity to L-asparaginase.

Read the detailed description

This open, randomized international Phase 2/3 study will enrol patients with relapsed ALL. The co-primary endpoints were the duration of asparagine depletion < 2µmol/L and the incidence of asparaginase hypersensitivity during induction. Key secondary endpoints are complete remission (CR), minimal residual disease (MRD), event free survival (EFS) and overall survival (OS).The study was powered to detect 3-fold difference in the incidence of allergic reactions between treatments. patients will be randomized to GRASPA or to Reference L-asparaginase. Patients with history of hypersensitivity to previous L-asparaginase treatment will be treated with GRASPA (exploratory arm)

Being tested
GRASPA, L-asparaginase
Keywords
acute lymphoblastic leukemia, relapse, asparaginase
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GRASPADrug

    Also called ERY001

    one injection of GRASPA 150 IU/kg at each cycle of chemotherapy

  • L-asparaginaseDrug

    Also called KIDROLASE

    3 to 4 Injections of Native E.coli asparaginase 10000IU/m² (every 3 days) at each cycle of chemotherapy

Study groups in NCT01518517
Study groupRoleWhat they receive
GRASPAExperimentalEach patient randomized in GRASPA® group is to receive at least 2 and up to 10 administration of GRASPA® 150 IU/kg, in combination with standard chemotherapy (COOPRALL). GRASPA® administration takes place as below: * for induction phase: at Day 4 and D18 (F1-F2 induction ) or at D6 if Vanda induction applies (according disease severity) * for consolidation phase: at Day 6 of R2 / R1 blocks, each time block of chemotherapy is given (up to 8 cycles)
Receives: Drug: GRASPA
reference L-asparaginaseActive comparatorFor patient randomized in control group, reference L-asparaginase 10,000 IU/m² will be administered every 3 days intravenously, in combination with standard chemotherapy (COOPRALL). •for induction phase:at Day 4 , D7, D10, D13 (F1 block ) then at Day 18, D21, D24, D27 (of F2 Blocks). NB: administrations take place at D6, D9, D12 and D15 in case of F1-F2 Induction is replaced by VANDA (according disease severity) •for consolidation phase: at D6, D9, D12 ofR2/R1 blocks, each time block of chemotherapy is given (up to 8 cycles).
Receives: Drug: L-asparaginase

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration of Asparaginase Activity >100 U/L During Induction

    Co-primary efficacy endpoint: duration in days of asparaginase activity >100 U/L in whole blood during the induction treatment phase: last available date/time of activity >100 UI/L before activity drops below 100 U/L - date/time of first activity >100 UI/L. Asparaginase activity is compared for GRASPA versus native ASNase to demonstrate the non-inferiority of GRASPA.

    Measured: Induction treatment period (i.e. 28 days)

  2. Allergic Reaction During Induction Phase

    Co-primary safety endpoint: allergic reaction regardless of grade during induction phase. Only those reactions that were reported in relation to the treatment to which the patient was randomised were counted.

    Measured: Induction treatment period (i.e. 28 days)

Secondary outcomes (3)

  1. Complete Remission (CR)

    CR is defined as, no physical evidence of leukemia, normal CBC, cytologic remission: normally regenerating bone marrow, with <5% leukemic blasts and the absence of detectable CNS or extramedullary disease, evaluated with physical examination and CSF findings, at the end of induction

    Measured: Induction treatment period (i.e. 28 days)

  2. Overall Survival (OS)

    OS is defined as the time from randomisation or date of inclusion (allergic arm) until death due to any cause. Patients who did not die were censored at 36 months of follow-up or the date of the patient's last visit, whichever was earlier.

    Measured: Overall trial period to 36 months

  3. Event Free Survival

    EFS is defined as the time from randomisation until the first documented sign of disease relapse or death due to any cause. In line with CHMP guidance (CHMP, 2016), patients who did not achieve CR at the end of the induction period were considered to have had an event at time 0. For the patients enrolled in the GRASPA allergic arm, EFS is defined from the date of inclusion in the study.

    Patients who achieved CR at the end of induction and who did not have a documented relapse or death due to any cause were censored at 36 months of follow-up or the date of the patient's last visit, whichever was earlier.

    Measured: Overall trial period to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2012 (estimated)
  2. Study startDec 2009
  3. Primary completionSep 2014
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01518517
Sponsor's protocol ID
GRASPALL2009-06
Acronym
GRASPIVOTALL
Status last verified
Feb 2022
First submitted
10 Jan 2012
Last updated
2 Feb 2022
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing GRASPA and L-asparaginase in people with Acute Lymphoblastic Leukemia, in Relapse, run by ERYtech Pharma at 28 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of Asparaginase Activity >100 U/L During Induction (time frame: Induction treatment period (i.e. 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01518517.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2022.

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